Personalized anticancer vaccines (VAP) are being developed to help the immune system target any remaining cancer cells in patients who have already received treatment. Unlike preventive vaccines, which aim to stop diseases like cancer before they start—such as those for human papillomavirus (HPV) or hepatitis B—personalized vaccines are used after cancer has been diagnosed, often after surgery to remove a tumor. These vaccines are designed specifically for each patient based on the unique molecular features of their tumor. Advances in high-throughput sequencing, bioinformatics, and messenger RNA (mRNA) vaccine technology have made it possible to create these highly customized treatments. Recent phase III clinical trials in the treatment of melanoma, a type of skin cancer, showed promising results. In August 2026, pharmaceutical companies Merck and Moderna announced that patients with stage III or IV melanoma who received a personalized neoantigen vaccine (intismeran autogene or V940) along with pembrolizumab—an immunotherapy drug—had longer periods without cancer recurrence after surgery compared to those who did not get the vaccine. However, full details of the trial and its safety profile have not yet been published. The process of selecting neoantigens—unique proteins found on cancer cells that can activate the immune system—involves identifying genetic mutations in the tumor that produce peptides capable of triggering T cells. This requires whole exome sequencing, HLA typing (which identifies proteins on the surface of cells that help the immune system recognize foreign substances), and the use of algorithms to predict which peptides are likely to be recognized by the immune system. Despite these advances, predicting which peptides will actually trigger an immune response remains a challenge, as HLA binding alone does not guarantee that a peptide will be effective. Vaccines can be delivered using various platforms, including peptide vaccines, mRNA vaccines, DNA vaccines, viral vectors, and dendritic cell vaccines. Among these, mRNA vaccines are the most advanced in clinical use, offering benefits like the absence of genome integration and faster production. However, the choice of platform can significantly affect the vaccine's effectiveness. Preliminary results for personalized vaccines in melanoma have been encouraging. A 2017 study showed that a vaccine containing up to 20 neoantigens could generate strong immune responses. A phase IIb trial, Keynote-942, found that combining the mRNA vaccine autogene intismeran with pembrolizumab improved the time before cancer returned. These findings led to the phase III INTerpath-001 trial, which successfully met its main goals. However, a phase II trial testing autogene cevumeran in colorectal cancer was halted in August 2026 after an unexpected increase in deaths among patients receiving the experimental treatment. Despite the promise of personalized anticancer vaccines, several challenges remain. These include the need for standardized protocols, high costs associated with genetic sequencing and individualized production, and potential delays in vaccine delivery. While these vaccines are generally well tolerated, with common side effects like injection site reactions and flu-like symptoms, there is still concern about the risk of the immune system attacking healthy cells. More research is needed to determine which cancers and patients will benefit most, how to improve the identification of effective neoantigens, and how to make this form of treatment faster, more reliable, and more affordable.